Second Universal Definition of HF Focuses on Phenotypes and Etiology

With more diverse phenotypes of heart failure (HF) having been identified, a group of experts has created the second universal definition of HF to further standardize descriptions, refine disease stages, and propose a classification of causes.

The new work builds on and reaffirms the first universal definition of HF, which was proposed in 2021. That definition clarified previously ambiguous terminology and proposed revised stages of the HF continuum, including pre-HF (stage B).

“We know that over time, including since the first universal definition, the prevalence of heart failure continues to grow around the world,” Mary Norine Walsh, MD (Ascension St. Vincent Heart Center, Indianapolis, IN), co-chair of the writing group for the new consensus, told TCTMD. “This document is an attempt to address that and to focus on early stages of disease, emphasizing the importance of identifying people at risk, or in the early stages of heart failure, before their symptoms are detected.”

Developed by representatives of the American Heart Association (AHA), American College of Cardiology (ACC), European Society of Cardiology, and World Heart Federation, in collaboration with other groups, the second universal definition makes its mark by moving away from specific left ventricular ejection fraction (LVEF) cutoffs in favor of simplifying HF classification into three clinically actionable groups: HF with ejection fraction that is reduced (HFrEF), improved (HFimpEF), and preserved (HFpEF).

The committee states that the primary motivation for the change was that the first universal definition used LVEF cutoffs that were arbitrary, “with the known variability of echocardiographic measurements of LVEF, difficulties in [interpreting] LVEF measured with different imaging modalities, and remaining debate over whether LVEF cutoffs should account for differences by sex, age, and ethnicity.” An exact LVEF cutoff, they conclude, may not be identical from one patient to another.

To TCTMD, Walsh noted that patients with previously reduced LVEF that has now increased or normalized, a condition called HFimpEF first introduced in the 2022 guideline from the ACC, AHA, and Heart Failure Society of America, represent an important and fluid group that researchers are still learning about.

“It’s very different than heart failure with persistent low ejection fraction, and it’s certainly very different from heart failure that started out with more preserved ejection fraction,” she explained. “This is a category of patients who on guideline-directed medical therapy—whatever that has been, either medical therapy or device therapy—have improved ejection fraction, and this is a group of patients we have to continue to monitor clinically both with imaging and also follow-up to make certain that their clinical status remains improved.”

Importantly, improvement in EF does not signify disease resolution, nor is it the same as stable heart failure, the committee notes. HFimpEF patients continue to have a diagnosis of HF and remain at risk for recurrent left ventricular dysfunction, hospitalization, and sudden cardiac death, which is why they must be maintained on guideline-directed medical therapy with longitudinal clinical surveillance.

Classification of Causes

Also in the consensus document, which was published online this week in JACC, Circulation, the European Heart Journal, and Global Heart, Walsh and the rest of the committee stress the importance of classifying HF by cause, but with expansion beyond ischemic and nonischemic cardiomyopathy. They note that having only two categories omits many of the causes of dilated and hypertrophic cardiomyopathies and “does not acknowledge the impact of identifying specific causes on treatment.”

One example of this would be a patient with cardiac amyloidosis as the underlying cause of HF who would benefit from targeted treatment for it beyond conventional HF therapies.

The second universal definition of HF breaks down the cardiomyopathy-based causes into pathogenic groups independent of LVEF, providing common examples of each. They are: ischemic, hypertensive, valvular, arrhythmia-related, infiltrative, infective, inflammatory, toxic, heritable, pericardial, metabolic and nutritional, pregnancy-related, stress-induced, pulmonary/right-sided heart disease, congenital, high-output mediated, other, and idiopathic.

“The consideration of key HF causes encourages targeted application of appropriate diagnostic and treatment strategies that prevent the development and progression of HF in individuals with specific identifiable causes,” the authors write. As deep phenotyping of HF advances, they suggest that “specific examples may be reclassified with better understanding of the underlying pathogenic processes; for instance, some forms of idiopathic cardiomyopathy may be reclassified as genetic/familial cardiomyopathy as underlying genetic variants are discovered.”

Trajectories of HF and Personalized Risk Reduction

One of the key messages of the consensus document, Walsh said, is the evolving view that HF “is a condition that’s dynamic with potential for improvement, remission, or progression rather than viewing it as a fixed diagnosis.”

The potential for changing clinical trajectories over time is outlined, beginning with HF risk factors (stage A), pre-HF (stage B), and symptomatic HF (stage C). The authors note that stage C can take multiple forms. Patients within that stage can experience remission or LVEF improvements despite ongoing structural or clinical abnormalities, with some even moving on to remission or recovery, although they are in the minority. Likewise, stage C patients also can progress to advanced HF (stage D) or death.

This fluidity of trajectories falls in line with a recent European expert consensus document that emphasizes how disease progression in HF may be altered by early identification and targeted interventions.

Individualized risk reduction is a central theme of the new document, Walsh noted, and an important part of personalized care is the recognition of the importance of social determinants of health and geographic variation.

“It’s very clear that heart failure globally differs from region to region and country to country, and social determinants of health really matter with regard to access of care and outcomes,” Walsh noted. “And so I think certainly future documents of all kinds involving the care of patients with heart failure will need to focus on both of those factors. There’s clearly always going to be work to do and this document is not a guideline [but] is meant to work with the guidelines of the professional societies.”